The Shrimpers seemed to be coasting at 2-0 up going into the final stages of the match, but Nick Chadwick reduced arrears for Argyle before on-loan debutant Alex MacDonald levelled.
Chadwick found the net from 20 yards while MacDonald pounced from close range, after fellow substitute Joe Lennox's shot rebounded off the post, to secure a vital point for the Pilgrims.
The late comeback came after Southend enjoyed a flying start, as Michael Timlin prospered following a defensive mix-up to score after just 59 seconds.
Home keeper Jake Cole's attempted clearance of a back pass in slippery conditions was charged down by Timlin and the ball flew into the back of the net.
The visitors' joy was doubled in the 34th minute when David Martin crashed the ball in from close range after Liam Dickinson's shot was deflected but Plymouth would have the final say with their two late efforts.
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